To produce a 25 cM base genetic map in Pima Indians, we have genotyped over 150 highly heterozygous short tandem repeat polymorphisms, STRPs, scattered across the genome in a data set of 1000 individuals comprising 250 nuclear families. The average heterozygosity in Pima Indians is approximately 11% lower than the reported in Caucasians for these STRPs. Linkage analysis using these STRP markers revealed regions on chromsomes 1, 6, and 7 that show linkage to various aspects of carbohydrate or fat metabolism or show linkage to diabetes. We have genotyped additional markers in the regions of linkage, and have started the physical mapping of a region on chromosome 1 covering approximately 9 cM with a number of YAC clones which include the original marker which showed linkage. A number of genes have been placed on the physical map including Phosphoglucomutase, Acyl Co-A Dehydrogenase, c-jun, Janus Kinase and Phosphodiesterase 4B. In addition, a number of unknown cDNAs also are located on the physical map. A region on chromosome 20 showed strong linkage to the quantitative character, stature. Analysis of additional markers supports the original linkage observation. A candidate gene, the bone morphogenetic protein 2 gene, BMP2, lies in this region. We screened this gene for structural variation. No consistent changes were observed. Sequence analysis of these individuals identified a single nucleotide substitution not detected with SSCP. This results in the substitution of a glycine for a valine, which was not associated with differences in stature. Previous analysis of the candidate gene GLUT2 on chromosome 3q showed linkage to percent body fat. The candidate gene Apolipoprotein-D had been linked to obesity in a British population. SSCP and sequence analysis of the Apolipoprotein gene did not support sib-pair linkage observation of linkage between obesity and chromosome 3.